Impact of therapy with chlorambucil, fludarabine, or fludarabine plus chlorambucil on infections in patients with chronic lymphocytic leukemia: Intergroup Study Cancer and Leukemia Group B 9011

Purpose: We sought to determine whether therapy with single-agent fludarabi ne compared with chlorambucil alone or the combination of both agents had a n impact on the incidence and spectrum of infections among a series of prev iously untreated patients with B-cell chronic lymphocytic leukemia (CLL). Patients and Methods: Five hundred fifty-four previously untreated CLL pati ents with intermediate/high-risk Rai-stage disease were enrolled onto an in tergroup protocol. Patients were randomized to therapy with chlorambucil, f ludarabine, or fludarabine plus chlorambucil. Data pertaining to infection were available on 518 patients. Differences in infections among treatment a rms were tested with the Kruskal-Wallis, Wilcoxon, and chi (2) tests. Results: A total of 1,107 infections (241 major infections) occurred in 518 patients over the infection follow-up period (interval from study entry un til either reinstitution of initial therapy, therapy with a second agent, o r death). Patients treated with fludarabine plus chlorambucil had more infe ctions than those receiving either single agent (P < .0001). Comparing the two single-agent arms, there were more infections on the fludarabine arm (P = .055) per month of follow-up. Fludarabine therapy was associated with mo re major infections and more herpesvirus infections compared with chlorambu cil (P = .008 and P = .004, respectively). Rai stage and best response to t herapy were not associated with infection. A low serum immunoglobulin G was associated with number of infections (P = .02). Age was associated with in cidence of major infection in the combination arm (P = .004). Conclusion: Combination therapy with fludarabine plus chlorambucil resulted in significantly more infections than treatment with either single agent. Patients receiving single-agent fludarabine had more major infections and h erpesvirus infections compared with chlorambucil-treated patients. J Clin Oncol 19:3611-3621. (C) 2001 by American Society of Clinical Oncolog y.